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BACKGROUND AND AIM: Spleen stiffness measurement (SSM) is useful for assessing portal hypertension. It is unclear whether SSM values are appropriate because vibration-controlled transient elastography (VCTE) does not generate B-mode images. This study aimed to confirm whether the controlled attenuation parameter (CAP) measured in the spleen can predict the accuracy of SSM. METHODS: This retrospective study enrolled 349 patients who underwent SSM using VCTE from January 2012 to December 2020. Consecutive patients were classified into the pilot set (SSM and hepatic venous pressure gradient [HVPG] were measured) and the validation set (SSM was measured without HVPG). In the pilot set, scatter plots with a nonparametric contour line were created. Logistic regression analysis was performed to predict outliers outside the 50% contour line. RESULTS: The values of CAP could distinguish the outliers in scatter plots between the HPVG and SSM in both univariate and multivariate analyses (cutoff, 118 dB/m). The correlation of SSM with HVPG (r = 0.718; P < 0.001) was significantly better in the low CAP (≤118 dB/m) group than in the high CAP (>118 dB/m) group (r = 0.330; P < 0.001). The area under the receiver operating characteristic curve of SSM in predicting high-risk varices was better in the low CAP group than in all patients or in the high CAP group in the pilot set (0.881, 0.854, and 0.843, respectively) and in the validation set (0.893, 0.821, and 0.814, respectively). CONCLUSION: For patients with CAP <118 dB/m, SSM is a feasible predictor of HVPG.

DOI： 10.1002/jgh3.12647

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BACKGROUND: An unexpected recurrence of hepatocellular carcinoma (HCC) sometimes occurs in patients with hepatitis C virus (HCV) after treatment with direct-acting antivirals (DAAs). However, the characteristics of patients with HCC recurrence may differ depending on time after DAA treatment. We aimed to identify risk factors related to HCC recurrence according to time after DAA treatment. METHODS: Of 1663 patients with HCV treated with a DAA, 199 patients had a previous history of HCC. We defined HCC recurrence within 1 year after DAA treatment as 'early recurrence', and recurrence more than 1 year after as 'late recurrence'. The different risk factors between the early and late phases of HCC recurrence after the end of DAA therapy were investigated. RESULTS: Ninety-seven patients experienced HCC recurrence during the study period. Incidences of recurrence were 29.8, 41.0, and 53.4% at 1, 2, and 3 years, respectively, after the end of DAA therapy. Multivariate analysis identified post-treatment α-fetoprotein (AFP) as an independent factor contributing to HCC recurrence in the early phase (hazard ratio, 1.056; 95% confidence interval, 1.026-1.087, p < 0.001) and post-treatment estimated glomerular filtration rate (eGFR) (hazard ratio, 0.98; 95% confidence interval, 0.96-0.99, p = 0.032) as a predictor of HCC recurrence in the late phase. CONCLUSION: Patients with higher post-treatment AFP in the early phase and those with lower post-treatment eGFR in the late phase had a high risk of HCC recurrence. The risk factors associated with HCC recurrence after DAA treatment were different between the early and late phases.

DOI： 10.1186/s12885-021-08401-7

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Endoplasmic reticulum (ER) stress plays an important role in hepatocyte degeneration, especially in patients with chronic liver injury. Protein kinase R-like endoplasmic reticulum kinase (PERK) is a key molecule in ER stress. PERK may contribute to apoptotic cell death in HCC, however the details of the mechanism are not clear. In this study, we identified PERK-associated molecules using transcriptome analysis. We modulated PERK expression using a plasmid, tunicamycin and siRNA against PERK, and then confirmed the target gene expression with real-time PCR and Northern blotting. We further analyzed the apoptotic function. Transcriptome analysis revealed that expression of the RNA component of mitochondrial RNA processing endoribonuclease (RMRP), which is a long noncoding RNA, was strongly correlated with the function of PERK. The expression of RMRP was correlated with the expression of PERK in experiments with the siRNA and PERK plasmid in both HCC cell lines and human HCC tissue. Furthermore, RMRP downregulation induced apoptotic cell death. RMRP is downregulated by PERK, which induces apoptosis in HCC. RMRP could be a new therapeutic target to regulate HCC in patients with chronic liver diseases associated with ER stress.

DOI： 10.1038/s41598-021-86592-6

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AIM: Liver stiffness measured using transient elastography (TE) is affected by tissue viscosity. The role of intrahepatic lymphatic fluid in liver stiffness is unclear. The present study aimed to investigate the effects of lymphatic vessel dilatation on liver stiffness. METHODS: Patients with chronic liver disease (n = 116) were enrolled from June 2018 to March 2020. All specimens were acquired by laparoscopic liver biopsy. Biopsy samples were stained with D2-40 for lymphatic vessel quantification based on a five-point scale for each specimen. Independent associations of liver stiffness measured by TE, strain elasticity (liver fibrosis index), and controlled attenuation parameter with fibrosis, lymphatic vessels, alanine aminotransferase, bilirubin, and steatosis were evaluated. RESULTS: Fibrosis, splenic stiffness measurement, and splenic volume were significantly correlated with the area of lymphatic vessels. Fibrosis, lymphatic vessels, and alanine aminotransferase were independent factors significantly associated with liver stiffness measurement (LSM; standardized coefficient [β] = 0.375, P < 0.001; β = 0.342, P < 0.001; and β = 0.359, P < 0.001, respectively). Fibrosis was the only independent factor significantly associated with liver fibrosis index (β = 0.360, P < 0.001), whereas the fat deposit area was the only independent factor significantly associated with controlled attenuation parameter (β = 0.455, P < 0.001). The areas under the receiver operating characteristic curves for diagnosing controlled ascites based on LSM, liver fibrosis index, splenic stiffness measurement, collagen proportionate area, and area of lymphatic vessels were 0.94, 0.66, 0.76, 0.64, and 0.79, respectively. CONCLUSIONS: Lymphatic vessel dilatation can affect liver stiffness measured using TE. Liver stiffness measurement is a predictive factor for ascites.

DOI： 10.1111/hepr.13610

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BACKGROUND: Hepatic venous pressure gradient (HVPG) is the gold standard index for evaluating portal hypertension; however, measuring HVPG is invasive. Although transient elastography (TE) is the most common procedure for evaluating organ stiffness, accurate measurement of spleen stiffness (SS) is difficult. We developed a device to demonstrate the diagnostic precision of TE and suggest this technique as a valuable new method to measure SS. METHODS: Of 292 consecutive patients enrolled in this single-centre, translational, cross-sectional study from June through September in 2019, 200 underwent SS measurement (SSM) using an M probe (training set, n = 130; inspection set, n = 70). We performed TE with B-mode imaging using an ultrasound-fusion method, printed new devices with a three-dimensional printer, and attached the magnetic position sensor to the convex and M probes. We evaluated the diagnostic precision of TE to evaluate the risk of esophagogastric varices (EGVs). RESULTS: The median spleen volume was 245 mL (range, 64-1,720 mL), and it took 2 minutes to acquire a B-mode image using the ultrasound-fusion method. The median success rates of TE were 83.3% and 57.6% in patients with and without the new device, respectively (p<0.001); it was 76.9% and 35.0% in patients with and without splenomegaly (<100 mL), respectively (p<0.001). In the prediction of EGVs, the areas under the receiver operating characteristic curve were 0.921 and 0.858 in patients with and without the new device, respectively (p = 0.043). When the new device was attached, the positive and negative likelihood ratios were 3.44 and 0.11, respectively. The cut-off value of SSM was 46.0 kPa. Data that were similar between the validation and training sets were obtained. CONCLUSIONS: The SS can be precisely measured using this new device with TE and ultrasound-fusion method. Similarly, we can estimate the bleeding risk due to EGV using this method.

DOI： 10.1371/journal.pone.0246315

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Hyperammonemia is an important stimulator of myostatin expression, a negative regulator of muscle growth. After splenectomy or partial splenic artery embolization (PSE), hyperammonemia often improves. Thus, we investigated changes in skeletal muscle index (SMI) in patients following an operation on the spleen and in patients who did not undergo an operation on their spleen. The study was designed retrospectively, in which we analyzed data collected between January 2000 and December 2015. Patients were assigned to the splenectomy/PSE or nontreatment group. Changes in SMI (ΔSMI), ammonia (Δammonia), myostatin (Δmyostatin), irisin (Δirisin), and branched-chain amino acids/tyrosine molar ratio (ΔBTR) were analyzed between baseline and 5-year follow-up both before and after inverse probability of treatment weighting adjustment (IPTW). Patients (102) were enrolled (splenectomy/PSE, n = 45; nontreatment group, n = 57) before IPTW adjustment: ΔSMI (2.6 cm2/m2 vs. -8.8 cm2/m2, respectively) (P < 0.001), Δmyostatin (-867 vs. -568, respectively) (P < 0.001), Δammonia (-34 and 16, respectively) (P < 0.001), and ΔBTR (0.89 and -0.665, respectively) (P < 0.001). There were no differences between splenectomy and PSE regarding these factors. Moreover, after IPTW adjustment, significant differences were observed between the splenectomy/PSE and nontreatment group for the median ΔBTR (0.89 and -0.64, respectively) (P < 0.001), Δammonia (-33 and 16, respectively) (P < 0.001), Δmyostatin (-894 and 504, respectively) (P < 0.001), and ΔSMI (1.8 cm2/m2 and -8.2 cm2/m2, respectively) (P < 0.001). Conclusions: Both splenectomy and PSE were associated with the prevention of secondary sarcopenia in patients with LC. Moreover, it can be expected that muscle volume loss is reduced by splenectomy or PSE in patients with hyperammonemia.

DOI： 10.1002/hep4.1604

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Sex differences in the predictors for hepatocellular carcinoma (HCC) development after direct-acting antiviral (DAA) therapy was investigated. DAA therapy was given to 1438 (663 male, 775 female) patients. Sex differences in the HCC development rate and the factors contributing to HCC development after DAA therapy were investigated. Male patients had a significantly higher cumulative HCC incidence (log-rank test, P =  .007). On multivariate analysis, the fibrosis-4 index (HR = 1.11; 95%CI, 1.042-1.202, P =  .002) and posttreatment α-fetoprotein (AFP) (HR = 1.11; 95%CI, 1.046-1.197, P  =  .001) were found to be independent factors that contributed to HCC development following DAA therapy in female patients, whereas only posttreatment AFP (HR  =  1.090; 95%CI, 1.024-1.160, P  = .007) was an independent factor in male patients. The optimal posttreatment AFP cut-off values were set based on receiver operating characteristic curve analyses. The optimal posttreatment AFP cut-off value was much higher in females (6.0 ng/mL) than in male (3.5 ng/mL) patients. In conclusion both in male and female patients, posttreatment AFP was an independent predictor of HCC development after DAA therapy. However, the cut-off values differed between the sexes. In male patients, HCC could be seen in patients with relatively low posttreatment AFP levels; more careful observation might be needed in such patients.

DOI： 10.1002/jmv.25984

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BACKGROUND AND AIMS: Lipoprotein(a) [Lp(a)] is an important independent cardiovascular risk factor. However, Lp(a) levels are lower in patients with chronic liver disease than in healthy subjects. Furthermore, Lp(a) levels decrease as residual liver function declines. Although non-alcoholic fatty liver disease (NAFLD), especially advanced non-alcoholic steatohepatitis (NASH), increases the risk of cardiovascular diseases, the relationship between serum Lp(a) level and NASH is unknown. Thus, we examined the relationship between serum Lp(a) levels and biopsy-proved NAFLD and clarified the significance of Lp(a) measurements for cardiovascular disease screening in patients with NAFLD. METHODS: A total of 176 patients with NAFLD were enrolled. Comprehensive blood chemistry tests and histological examinations of liver samples were conducted. The relationship between serum Lp(a) levels and NAFLD was analyzed. RESULTS: Serum Lp(a) levels in advanced fibrosis (stage 3-4) were lower than those in non-advanced fibrosis (stage 0-2) (p < 0.05). After adjustment for age, sex, body mass index, alanine aminotransferase (ALT), creatinine (Cre), HbA1c level, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and the use of lipid-lowering agents, the significant inverse association between advanced fibrosis and serum Lp(a) levels remained (p < 0.01). Although the Lp(a) level was inversely associated with an NAFLD Activity Score (NAS) of 5-8, there was no significant association between Lp(a) levels and NAS adjusted for age, sex, body mass index, ALT, Cre, HbA1c level, HDL-C, LDL-C, TG, and the use of lipid-lowering agents. CONCLUSIONS: Advanced NASH is associated with low serum Lp(a) levels; therefore, Lp(a) levels may not be useful in evaluating cardiovascular risk.

DOI： 10.1016/j.atherosclerosis.2020.02.026

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DOI： 10.2169/internalmedicine.3886-19

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BACKGROUND AND AIM: Certain thrombocytopenic patients with chronic liver disease have inadequate platelet count recovery after platelet transfusion or lusutrombopag administration. We aimed to identify the reasons for this phenomenon. METHODS: We investigated 58 and 86 thrombocytopenic patients with chronic liver disease who received lusutrombopag (3 mg orally for up to 7 days) or underwent blood transfusions, respectively. Thirty patients underwent simultaneous hepatic surgery and splenectomy. Factors preventing platelet count recovery above 50 × 103 /μL were identified. RESULTS: The median patient age was 64 years. Eleven, 78, and 55 patients had hepatitis B, hepatitis C, or another etiology, respectively; 59, 69, and 16 had Child-Pugh classes A, B, and C, respectively. The median spleen volume was 432 mL, and a median of 10 blood units were transfused per patient. The median platelet count rose significantly (from 41.5 × 103 /μL to 81.0 × 103 /μL) after lusutrombopag administration but not after blood transfusion before invasive procedures. However, maximum platelet counts in patients who underwent splenectomy before platelet transfusion were markedly improved over those who did not. Increasing platelet counts above 50 × 103 /μL required baseline platelets > 30 × 103 /μL and lusutrombopag administration for all patients. Platelet count recovery was dependent on a spleen volume of < 300 mL and baseline platelets of > 40 × 103 /μL in patients who underwent platelet transfusions, while a baseline platelet count of > 30 × 103 /μL was required for patients administered with lusutrombopag. CONCLUSION: Neither blood transfusion nor lusutrombopag improves thrombocytopenia in patients with severe conditions; however, the degree of platelet count elevation following lusutrombopag administration is higher than that following blood transfusion.

DOI： 10.1111/jgh.14786

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Objective The long-term effect of the ABO blood type on the clinical course of patients with pancreatic cancer (PC) is inconclusive. This study aimed to determine whether or not the ABO blood type influences the long-term outcomes of PC in Japanese patients. Methods The medical records of Japanese patients with PC were reviewed. Data, including the age, sex, and outcomes, from the Ehime Pancreato-Cholangiology Study Group were analyzed. Results The mean age of the 406 patients was 71.0±10.5 years, and 220 (54.2%) were men. A total of 44.6%, 20.7%, 22.4%, and 12.3% had blood type A, B, O, and AB, respectively. The median survival time (MST) of patients with A alleles was shorter than that of patients with non-A alleles (p=0.048), especially among those who underwent resection (p=0.031). In contrast, no marked difference in the MST was noted among those who underwent chemotherapy and palliative care. Finally, a multivariate analysis confirmed A alleles as an independent factor associated with the long-term outcome of PC (p<0.05 in 2 different models). Conclusion The ABO blood type influenced the long-term outcomes of Japanese patients with PC, presumably due to its impact on disease onset and tumor behavior.

DOI： 10.2169/internalmedicine.3748-19

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In the original publication of the article the formula under the heading "Three-point method" was incorrect, the correct formula is given in this correction.

DOI： 10.1007/s10396-019-00966-y

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OBJECTIVE: To evaluate whether patients with hepatitis B virus (HBV)- and hepatitis C virus (HCV)-related chronic liver disease were diagnosed as having pancreatic cancer (PC) at an early stage during abdominal imaging surveillance for hepatocellular carcinoma (HCC). PATIENTS AND METHODS: We retrospectively examined 447 patients with PC diagnosed at Ehime University Hospital and affiliated centers (2011-2013). Data were collected regarding HBV and HCV status, likelihood of PC diagnosis, and Union for International Cancer Control (UICC) stage. Intergroup comparisons were performed using the χ2 test. RESULTS: The UICC stage distribution in the HCC surveillance group (n=16) was stage 0 (n=2, 12.5%), stage IA (n=3, 18.8%), stage IB (n=2, 12.5%), stage IIA (n=2, 12.5%), stage IIB (n=2, 12.5%), stage III (n=1, 6.3%), and stage IV (n=4, 25%). The UICC stage distribution in the nonsurveillance group (n=431) was stage 0 (n=4, 0.9%), stage IA (n=28, 6.5%), stage IB (n=27, 6.3%), stage IIA (n=86, 20.0%), stage IIB (n=48, 11.1%), stage III (n=56, 13.0%), and stage IV (n=182, 42.2%). The HCC surveillance group had significantly more patients with stage 0 disease than with stages IA through IV (P=.02). Similar results were observed when including stages IA (P=.007) and IB (P=.004) as early stages but not stage IIA (P=.10). A dilated pancreatic duct led to a PC diagnosis in all 6 patients with stage 0 disease. CONCLUSION: Patients with HBV- and HCV-related chronic liver disease had an early PC diagnosis during HCC surveillance. Careful evaluation of the pancreas is warranted during HCC surveillance.

DOI： 10.1016/j.mayocp.2018.12.034

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Lenvatinib has anti-tumor activity against advanced hepatocellular carcinoma (HCC). Hypothyroidism is also a frequent complication in patients treated with lenvatinib. However, studies on lenvatinib-induced thyroid toxicity and destructive thyroiditis are limited. Therefore, this study aimed to clarify the frequency and timing of thyroid abnormalities in lenvatinib for unresectable HCC. This retrospective study enrolled 50 patients with advanced HCC treated with lenvatinib. Patients were classified to have euthyroid, subclinical hypothyroidism, overt hypothyroidism, and thyrotoxicosis. The timing of thyroid dysfunction was assessed, and risk factors for incident hypothyroidism or thyrotoxicosis were evaluated using multivariate models. Subclinical hypothyroidism, overt hypothyroidism, and thyrotoxicosis occurred in 7 (14.0%), 26 (52.0%), and 5 (10.0%) patients, respectively. In the 33 patients with hypothyroidism, 27 (84.4%) developed the condition within 2 weeks of starting lenvatinib treatment. Of the 5 patients with thyrotoxicosis, 3 developed the condition within 8 weeks of starting lenvatinib administration. One patient developed thyrotoxicosis in only 1 week of the initiation of treatment. No correlation between the presence of antibodies and the incidence and severity of thyroid dysfunction due to the autoimmune mechanism was observed. The progression-free survival was significantly better in the hypothyroidism group. Lenvatinib treatment for unresectable HCC not only causes hypothyroidism, but also thyrotoxicosis. Moreover, these thyroid conditions develop within the early period of treatment at a higher prevalence. Patients with thyroid dysfunction had better prognosis. Based on these results, in patients administered with lenvatinib, there is need for careful assessment for the possibility of thyroid dysfunction from the onset of treatment.

DOI： 10.1507/endocrj.EJ19-0140

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Schistosomiasis infection is a major cause of morbidity and mortality in endemic areas. Developed countries have declared that schistosomiasis has been eradicated; however, residents of these countries may travel and stay in endemic areas and the number of foreign travelers is increasing in the recent years. Thus, schistosomiasis is regarded as an imported infection. Ultrasonography and serum antibody titer tests are well established as diagnostic methods for schistosomiasis. However, a definitive diagnosis cannot be obtained using these tests in some cases. We herein report a case in which schistosomiasis was confirmed based on laparoscopic liver biopsy without a definitive diagnosis by blood test, fecal examination, or imaging.

DOI： 10.2169/internalmedicine.2776-19

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AIM: The predictors for the development of hepatocellular carcinoma (HCC) after direct-acting antiviral (DAA) treatment were investigated. METHODS: A total of 1174 patients with chronic hepatitis C virus infection were treated with DAA therapy (sofosbuvir and ledipasvir [n = 615], sofosbuvir and ribavirin [n = 380], and daclatasvir and asunaprevir [n = 179]) and achieved sustained virologic response (SVR). The HCC development rate and the factors that might contribute to the development of HCC after the end of DAA treatment were analyzed. RESULTS: During the median observation period of 537 days, HCC developed in 33 cases. The incidence of HCC was 1.9%, 3.2%, and 4.1% at 1, 1.5, and 2 years after the end of DAA therapy, respectively. Multivariate analysis with pre- and post-treatment factors identified the Fibrosis-4 (FIB-4) index (hazard ratio [HR] = 1.09; 95% confidence interval [CI], 1.021-1.178; P = 0.011) and post-treatment α-fetoprotein (AFP) (HR = 1.11; 95% CI, 1.054-1.172; P < 0.001) as independent factors that contributed to the development of HCC after DAA therapy. Using these identified parameters, a new scoring system (0 to 2 points) was established. Patients in the high-score group (2 points) could be identified as having a significantly higher risk of HCC development, and the respective 1- and 2-year cumulative incidence rates of HCC were 6.1% and 14.4%. CONCLUSIONS: A high FIB-4 index and a high post-treatment AFP at the end of DAA treatment were the independent predictors for developing HCC after DAA treatment. For patients with these risk factors, extra attention to the possibility of HCC development is needed.

DOI： 10.1111/hepr.13278

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BACKGROUND: Although sorafenib-regorafenib sequential therapy improves the prognosis of patients with hepatocellular carcinoma (HCC), many patients abandon sequential therapy due to worsening hepatic reserve function. Thus, it is important to clarify which patients can be treated using regorafenib. The albumin-bilirubin score is a good biomarker for hepatic reserve function. The aim of this study was to determine whether patient albumin-bilirubin scores at the start of sorafenib treatment could be used to identify candidates for subsequent regorafenib therapy. METHODS: This is a retrospective cohort study. From 2009 to 2017, 267 hepatocellular carcinoma patients treated with sorafenib were enrolled. After sorafenib therapy, 138 progressive disease patients were analyzed. The patients were divided in two groups: (i) regorafenib candidate group (Child-Pugh class A, Eastern Cooperative Oncology Group Performance Status ≤1, and maintained sorafenib tolerance); and (ii) regorafenib non-candidate group. The primary endpoint was the albumin-bilirubin score. We assessed retrospectively whether albumin-bilirubin scores were useful for predicting regorafenib treatment regimen candidacy. RESULTS: For the 138 analyzed patients, the median overall survival duration was 15.6 months in the regorafenib candidate group and 6.8 months in the regorafenib non-candidate group (P < 0.01). Using univariate analysis, etiology, aspartate aminotransferase ≥40 IU/L, prothrombin time ≥85% and albumin-bilirubin score <-2.53 at the start of sorafenib treatment were identified as predictors. Using multivariate analysis, albumin-bilirubin score <-2.53 was the only significant predictor. CONCLUSIONS: Based on the multivariate analysis results, albumin-bilirubin score at the start of sorafenib therapy is a useful marker for identifying candidate patients for starting regorafenib therapy.

DOI： 10.1093/jjco/hyy153

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Hepatic stellate cells (HSCs) were reported to promote the progression of hepatocellular carcinoma (HCC), however its mechanism is uncertain. We previously reported that protein kinase R (PKR) in hepatocytes regulated HCC proliferation. In this study, we focused on the role of PKR in HSCs, and clarified the mechanism of its association with HCC progression. We confirmed the activation of PKR in a human HSC cell line (LX-2 cell). IL-1β is produced from HSCs stimulated by lipopolysaccharide (LPS) or palmitic acid which are likely activators of PKR in non-alcoholic steatohepatitis (NASH). Production was assessed by real-time PCR and ELISA. C16 and small interfering RNA (siRNA) were used to inhibit PKR in HSCs. The HCC cell line (HepG2 cell) was cultured with HSC conditioning medium to assess HCC progression, which was evaluated by proliferation and scratch assays. Expression of PKR was increased and activated in stimulated HSCs, and IL-1β production was also increased molecular. Key molecules of the mitogen-activated protein kinase pathway were also upregulated and activated by LPS. Otherwise, PKR inhibition by C16 and PKR siRNA decreased IL-1β production. HCC progression was promoted by HSC-stimulated conditioning medium although it was reduced by the conditioning medium from PKR-inhibited HSCs. Moreover, palmitic acid also upregulated IL-1β expression in HSCs, and conditioning medium from palmitic acid-stimulated HSCs promoted HCC proliferation. Stimulated HSCs by activators of PKR in NASH could play a role in promoting HCC progression through the production of IL-1β, via a mechanism that seems to be dependent on PKR activation.

DOI： 10.1371/journal.pone.0212589

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PURPOSE: The aim of this study was to clarify whether ultrasound quantitative methods were positively correlated with volume of ascites evaluated by whole abdominopelvic CT. METHODS: Sixty-eight patients with cirrhotic ascites were retrospectively analyzed. First, to confirm that virtual ultrasonography (VUS) is an alternative method to conventional ultrasound, 22 patients underwent both conventional ultrasonography and VUS. Second, the efficacy of US quantitative methods (3-point method, 4-point method, 5-point method, and Matsumoto's method) was confirmed by VUS in 68 patients. We assessed whether the ascites volume predicted by VUS corresponded with that calculated by 3D-CT. Of the 68 patients, 23 patients were analyzed before and after administration of tolvaptan. RESULTS: The predictive volumes calculated by VUS were remarkably relative to those yielded by conventional US. Correlations between exact volume and those measured by VUS were significantly high (3-point method: r = 0.882, p < 0.001; 4-point method: r = 0.797, p < 0.001; 5-point method: r = 0.836, p < 0.001; Matsumoto's method: r = 0.453, p < 0.001). Correlations between decreasing volume on 3D-CT and that measured by VUS were also significantly high in patients with administration of tolvaptan. CONCLUSION: Ascites volume measured by ultrasound was effective, especially the 3-point and 5-point methods. It was useful to assess the efficacy of diuretics in cirrhotic patients.

DOI： 10.1007/s10396-018-0879-9

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BACKGROUND AND AIM: The aim of this study is to confirm the efficacy of multipolar ablation with a new simulator system, three-dimensional (3-D) sim-Navigator, for patients with hepatocellular carcinoma by assessing relapse-free survival and shape of the ablation volume under clinical conditions. METHODS: All participants provided written, informed consent, and study protocols were approved by the institutional ethics committee. Twenty-seven patients with 27 nodules were treated by no-touch ablation using the new simulator system. Another 21 patients with 21 nodules treated without the simulator system were enrolled as controls. Tumor progression and shape of ablation volume were assessed. Predictors of tumor progression were assessed by Cox proportional hazard model. RESULTS: No significant differences in clinical characteristics were seen between groups. Mean sphericity was 0.48 ± 0.07 with 3-D sim-Navigator and 0.37 ± 0.07 without 3-D sim-Navigator (P < 0.001). Median surface-to-volume ratio and compactness were also significantly closer to those of a sphere with 3-D sim-Navigator (P = 0.017, P < 0.001). Relapse-free survival rates at 1 and 1.5 years were 94.1% and 82.4%, respectively, with 3-D sim-Navigator, compared with 83.2% and 55.5% without (P = 0.056). The only independent factor predicting relapse-free survival was use of 3-D sim-Navigator (hazard ratio, 0.12; 95%CI, 0.01-0.87; P = 0.035). CONCLUSIONS: Ideal ablation area was acquired by this simulation and navigation system in clinics. This system improved local tumor progression by facilitating appropriate insertion of multiple electrodes.

DOI： 10.1111/jgh.13772

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AIM: Assessing disease progression in patients with primary biliary cholangitis (PBC) is necessary in order to evaluate therapeutic effectiveness. Therefore, the aims of this study were to evaluate both the diagnostic accuracy of both real-time tissue elastography (RTE) and vibration-controlled transient elastography (VCTE), and the usefulness of hepatic and splenic elasticity as predictive markers for the progression of symptomatic PBC. METHODS: The study participants were 44 patients with PBC. We assessed hepatic and splenic elasticity using RTE and VCTE and measured serum markers related to fibrosis and hepatic and splenic blood flow using Doppler ultrasonography. We then compared RTE and VCTE for diagnostic accuracy. Patients with asymptomatic PBC were followed every 1-3 months. RESULTS: Both RTE and VCTE performed well and had superior diagnostic accuracy compared with biochemical markers. The areas under the receiver operating characteristic curve for RTE and VCTE were 0.92 and 0.92, 0.95 and 0.91, and 0.97 and 0.91 for F ≥ 2, F ≥ 3, and F = 4, respectively. During follow-up, nine patients (25.0%) developed liver-related symptoms. Multivariate analysis revealed that splenic elasticity assessed using RTE was a significant independent factor for the development of liver-related symptoms (odds ratio, 2.19; P = 0.024). CONCLUSIONS: Real-time tissue elastography offered better diagnostic accuracy for severe fibrosis and cholangitis than VCTE. Splenic elasticity determined using RTE is a useful parameter for evaluating liver-related symptoms and an effective predictive marker of disease progression in patients with asymptomatic PBC.

DOI： 10.1111/hepr.12861

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A change in hepatic blood flow caused by the hepatic arterial buffer response (HABR) occurs as fatty liver disease progress. The aim of this longitudinal cohort study was to investigate whether fatty liver with the HABR induces metabolic disorders. In 2009 and 2010, 494 (89.5%) participants were enrolled. The median follow-up duration was 5.0 (interquartile range, 3.9-6.0) years. The hazard ratios of fatty liver with the HABR for incident metabolic disorders were assessed by Cox proportional hazard models. A non-fatty liver group (non-FL group, hepatorenal echo intensity ratio <1.12), a fatty liver without portal hypertension (FL group, hepatorenal echo intensity ratio ≥1.12 and ratio of the maximal blood velocity in the right hepatic artery to maximal blood velocity in the right portal vein <3.1) group, and a fatty liver with portal hypertension (FL-HABR group, hepatorenal echo intensity ratio ≥1.12 and ratio of the maximal blood velocity in the right hepatic artery to maximal blood velocity in the right portal vein ≥3.1) group were defined based on echo intensity and Doppler ultrasonography. Fatty liver with and without the HABR was significantly associated with the incidence of diabetes on multivariate analysis (non-FL versus FL group, hazard ratio, 3.36; 95% confidence interval, 1.05-12.85; FL versus FL with the HABR group, HR, 2.68; 95% confidence interval, 1.28-6.04). With respect to the incidence of hypertension and dyslipidemia, only FL with the HABR was a significant factor (hypertension, non-FL versus FL, P = 0.874, FL versus FL-HABR, P = 0.016, non-FL versus FL-HABR, P = 0.023; dyslipidemia, non-FL versus FL, P = 0.311, FL versus FL-HABR, P = 0.194, non-FL versus FL-HABR, P = 0.038). Conclusion: Fatty liver with the HABR is a high-risk condition for metabolic diseases. (Hepatology Communications 2017;1:623-633).

DOI： 10.1002/hep4.1070

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Language：Japanese   Publishing type：Research paper (scientific journal)  

PubMed

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER  

DOI： 10.1016/S0618-8278(19)31636-6

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY  

Web of Science

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY  

Web of Science

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